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Introduction and methods
Background
Despite the availability of several HF therapies, morbidity and mortality in patients with HF remain high [1-3]. One of the reasons could be low adherence to or non-persistence with medication [4-7].
Aim of the study
The authors aimed to study initiation, adherence, and long-term persistence for 3 HF drug classes (beta-blocker (BB ), RAASi, and MRA) in a Norwegian nationwide cohort of HF patients.
Methods
Data of 54,899 patients aged 18–79 years who were newly diagnosed with HF from 2014 through 2020 and who survived ≥30 days were collected from the Norwegian Patient Registry. These data were then linked to the Norwegian Prescription Database, which contains information about prescription drugs dispensed from pharmacies. Patients were followed to the outcome of interest (death) or until December 2020.
Initiation (time to drug initiation), adherence, and long-term persistence (no treatment break >30 days) were calculated for the prescription of a BB, a RAASi (ACEi, ARB, or ARNI), and an MRA, as well as for dual and triple HF therapy. One-year adherence was measured as proportion of days covered (i.e., number of days on medication divided by number of days under observation) and adherence was defined as ≥80%. Because of local reimbursement criteria for prescription of ARNIs, the group of patients initiating an ARNI was studied separately. To evaluate the robustness of the findings, sensitivity analyses were performed.
Main results
Initiation
- In the first year following the HF diagnosis, 87% of the cohort were prescribed a HF drug: 75% a BB, 69% a RAASi, and 21% an MRA. In drug-naïve patients, these proportions were 61%, 55%, and 19%, respectively.
- Dual HF therapy was prescribed to 61% of the patients in the first year and triple HF therapy to 16%.
- There were no major changes in drug prescriptions by calendar year, except for an increase in MRA and particularly ARNI prescriptions each year from 2014 through 2020 and a minor reduction in initiation of a BB from 2019 to 2020.
Adherence
- In the first year following drug initiation, the proportion of adherent patients for BB, RAASi, ARNI, and MRA was 83%, 81%, 84%, and 61%, respectively.
- Of the patients initiating dual or triple HF therapy, 42% and 5%, respectively, were adherent to this treatment in the first year.
- The proportion of patients being adherent to an MRA increased from 58% in 2014 to 64% in 2019.
- A sensitivity analysis based on a fixed prescription length showed lower adherence to monotherapy with a BB (80%), a RAASi (80%), or an MRA (55%) but not an ARNI (88%); adherence to dual or triple HF therapy did not change.
Long-term persistence
- Two years after drug initiation, 58% of the patients were still prescribed a BB, 57% a RAASi, and 31% an MRA.
- After 5 years, these proportions were 38%, 37%, and 15%, respectively.
- In the RAASi group, 2- to 5-year persistence was higher for ARNIs than for ACEis and ARBs.
- In the sensitivity analysis based on fixed prescription length, persistence was lower for all 3 HF drug classes.
Conclusion
This Norwegian nationwide cohort study with longitudinal follow-up showed that 1-year adherence to dual or triple HF therapies was low in newly diagnosed HF patients (42% and 5%, respectively). In addition, 2- to 5 -year persistence was inadequate, with almost half of the patients discontinuing a RAASi or BB and two-thirds discontinuing an MRA within 2 years.
Although the authors did not investigate the reasons for non-prescription or non-adherence, they believe “[u]rgent efforts are needed to improve implementation of HF drug treatment with decision support to clinicians and patients and ensure broader access to structured multidisciplinary care, particularly addressing adherence of multiple drug therapies.”
References
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2. Arrigo M, Jessup M, Mullens W, Reza N, Shah AM, Sliwa K, et al. Acute heart failure. Nat Rev Dis Primers. 2020; 6: 16.
3. McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, et al. 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). With the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2022; 24: 4–131.
4. Bitar S, Agrinier N, Alla F, Rossignol P, Mebazaa A, Thilly N. Adherence to ESC guideline-recommended medications over a 36-month follow-up period after hospitalization for heart failure: Results from the EPICAL2 cohort study. Pharmacoepidemiol Drug Saf. 2019; 28: 1489–1500.
5. Gislason GH, Rasmussen JN, Abildstrom SZ, Schramm TK, Hansen ML, Buch P, et al. Persistent use of evidence-based pharmacotherapy in heart failure is associated with improved outcomes. Circulation. 2007; 116: 737–744.
6. Hood SR, Giazzon AJ, Seamon G, Lane KA, Wang J, Eckert GJ, et al. Association between medication adherence and the outcomes of heart failure. Pharmacotherapy. 2018; 38: 539–545.
7. Savarese G, Bodegard J, Norhammar A, Sartipy P, Thuresson M, Cowie MR, et al. Heart failure drug titration, discontinuation, mortality and heart failure hospitalization risk: A multinational observational study (US, UK and Sweden). Eur J Heart Fail. 2021; 23: 1499–1511.
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